Nuclear receptor co-activator 4 (NCOA4) acts as a selective cargo receptor that binds to ferritin, a cytoplasmic iron storage complex. By mediating ferritinophagy, NCOA4 regulates iron metabolism and releases free iron in the body, thus playing a crucial role in a variety of biological processes, including growth, development, and metabolism. Recent studies have shown that NCOA4-mediated ferritinophagy is closely associated with the occurrence and development of iron metabolism-related diseases, such as liver fibrosis, renal cell carcinoma, and neurodegenerative diseases. In addition, a number of clinical drugs have been identified to modulate NCOA4-mediated ferritinophagy, significantly affecting disease progression and treatment efficacy. This paper aims to review the current research progress on the role of NCOA4-mediated ferritinophagy in related diseases, in order to provide new ideas for targeted clinical therapy.
Humans ; Nuclear Receptor Coactivators/physiology* ; Ferritins/metabolism* ; Animals ; Neurodegenerative Diseases/metabolism* ; Iron/metabolism* ; Autophagy/physiology* ; Liver Cirrhosis/metabolism* ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/physiopathology*

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

During orthodontic treatment, clinical monitoring of patients is a crucial factor in determining treatment success. It aids in timely problem detection and resolution, ensuring adherence to the intended treatment plan. In recent years, digital technology has increasingly permeated orthodontic clinical diagnosis and treatment, facilitating clinical decision-making, treatment planning, and follow-up monitoring. This review summarizes recent advancements in digital technology for monitoring orthodontic tooth movement, related complications, and appliance-wearing compliance. It aims to provide insights for researchers and clinicians to enhance the application of digital technology in orthodontics, improve treatment outcomes, and optimize patient experience. The digitization of diagnostic data and the visualization of dental models make chair-side follow-up monitoring more convenient, accurate, and efficient. At the same time, the emergence of remote monitoring technology allows orthodontists to promptly identify oral health issues in patients and take corresponding measures. Furthermore, the multimodal data fusion method offers valuable insights into the monitoring of the root-alveolar relationship. Artificial intelligence technology has made initial strides in automating the identification of orthodontic tooth movement, associated complications, and patient compliance evaluation. Sensors are effective tools for monitoring patient adherence and providing data-driven support for clinical decision-making. The application of digital technology in orthodontic monitoring holds great promise. However, challenges like technical bottlenecks, ethical considerations, and patient acceptance remain.

Objective:To observe and analyze the ocular clinical features and pathogenic genes of horizontal gaze palsy with progressive scoliosis (HGPPS).Methods:A pedigree study was conducted.Two families with HGPPS diagnosed by ophthalmology examination at Henan Children's Hospital from November 2023 to April 2024 were included, with 3 people from two generations in each family.Medical history and family history of the subjects were inquired.Vision acuity, diopter, anterior segment, intraocular pressure, wide-angle laser scanning ophthalmoscopy, optical coherence tomography, visual evoked potential (VEP), electroretinogram (ERG), ocular B-ultrasound, full spine AP+ lateral view, orbit+ skull+ cervical spine+ thoracic spine+ lumbosacral spine MRI plain scan were performed on the subjects.Whole genomic DNA was extracted from 2 ml of peripheral venous blood collected from the subjects, and gene sequencing was performed using whole exome sequencing (WES) technology.Suspicious pathogenic variant loci were verified by Sanger sequencing, and the pathogenicity of gene variant loci was analyzed according to the ACMG standards and guidelines for the interpretation of sequence variants.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Ethics Committee of Henan Children's Hospital (No.2024-KY-0024).All subjects and guardians signed informed consent forms and were informed of relevant matters before genetic testing.Results:The proband from family 1 was male, 3 years and 2 months old.At the age of 6 months, he was found to have head tilted to the left with a right scoliosis of the spine centered on T11-12 and no obvious abnormalities on VEP and ERG examinations.The proband from family 2 was male, 3 years and 4 months old, with a left scoliosis of the spine centered on T12.Both probands developed horizontal fixation paralysis, unable to rotate eye outward, slightly limited inward rotation, left eye hypertropia, mild horizontal nystagmus, normal vertical eye movement, backward development of major movements, and normal vision, anterior segment and fundus.MRI examination showed that the medulla oblongata was butterfly shaped, and a brainstem fissure could be seen in the center of the medulla oblongata.The genetic testing showed that the proband from family 1 had compound heterozygous variations c. 1054delC/p.Gln352Serfs *90 (M1) in exon 7 and c. 1219G>T/p.Gly407Cys (M2) in exon 8 of ROBO3 gene.The father of the proband carried M1 and the mother of the proband carried M2.The proband from family 2 had compound heterozygous variations c. 1888C>T/p.R630X (M3) in exon 12 and c. 2684C>A/p.A895E (M4) in exon 17 of ROBO3 gene.M1 and M3 were possible pathogenic, and M2 and M4 were of unknown clinical significance, and prediction software predicted M2 and M4 were harmful variations. Conclusions:The main clinical features of two HGPPS pedigree are horizontal fixation paralysis and progressive scoliosis, accompanied by nystagmus and strabismus.MRI shows brainstem fissure in the central medullary area.Four variants are novel variants, which increases the variation spectrum of ROBO3 gene.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

Objective:To observe and analyze the ocular clinical features and pathogenic genes of horizontal gaze palsy with progressive scoliosis (HGPPS).Methods:A pedigree study was conducted.Two families with HGPPS diagnosed by ophthalmology examination at Henan Children's Hospital from November 2023 to April 2024 were included, with 3 people from two generations in each family.Medical history and family history of the subjects were inquired.Vision acuity, diopter, anterior segment, intraocular pressure, wide-angle laser scanning ophthalmoscopy, optical coherence tomography, visual evoked potential (VEP), electroretinogram (ERG), ocular B-ultrasound, full spine AP+ lateral view, orbit+ skull+ cervical spine+ thoracic spine+ lumbosacral spine MRI plain scan were performed on the subjects.Whole genomic DNA was extracted from 2 ml of peripheral venous blood collected from the subjects, and gene sequencing was performed using whole exome sequencing (WES) technology.Suspicious pathogenic variant loci were verified by Sanger sequencing, and the pathogenicity of gene variant loci was analyzed according to the ACMG standards and guidelines for the interpretation of sequence variants.This study followed the Declaration of Helsinki.The study protocol was reviewed and approved by the Ethics Committee of Henan Children's Hospital (No.2024-KY-0024).All subjects and guardians signed informed consent forms and were informed of relevant matters before genetic testing.Results:The proband from family 1 was male, 3 years and 2 months old.At the age of 6 months, he was found to have head tilted to the left with a right scoliosis of the spine centered on T11-12 and no obvious abnormalities on VEP and ERG examinations.The proband from family 2 was male, 3 years and 4 months old, with a left scoliosis of the spine centered on T12.Both probands developed horizontal fixation paralysis, unable to rotate eye outward, slightly limited inward rotation, left eye hypertropia, mild horizontal nystagmus, normal vertical eye movement, backward development of major movements, and normal vision, anterior segment and fundus.MRI examination showed that the medulla oblongata was butterfly shaped, and a brainstem fissure could be seen in the center of the medulla oblongata.The genetic testing showed that the proband from family 1 had compound heterozygous variations c. 1054delC/p.Gln352Serfs *90 (M1) in exon 7 and c. 1219G>T/p.Gly407Cys (M2) in exon 8 of ROBO3 gene.The father of the proband carried M1 and the mother of the proband carried M2.The proband from family 2 had compound heterozygous variations c. 1888C>T/p.R630X (M3) in exon 12 and c. 2684C>A/p.A895E (M4) in exon 17 of ROBO3 gene.M1 and M3 were possible pathogenic, and M2 and M4 were of unknown clinical significance, and prediction software predicted M2 and M4 were harmful variations. Conclusions:The main clinical features of two HGPPS pedigree are horizontal fixation paralysis and progressive scoliosis, accompanied by nystagmus and strabismus.MRI shows brainstem fissure in the central medullary area.Four variants are novel variants, which increases the variation spectrum of ROBO3 gene.

Fucoidan(FUC)is a natural seaweed-derived drug.Previously,our experiments have shown that FUC can significantly inhibit the cell viability of human osteosarcoma 143B cells and induce cell death,but the mechanism remains unclear.Ferroptosis,a novel form of cell death,has emerged as an important target for tumor therapy.This study aims to investigate whether FUC induces ferroptosis of 143B cells and elucidate its underlying molecular mechanisms.CCK-8 and LDH assays result showed that FUC(10,100,400 μg/mL)significantly reduced cell viability of 143B cells and induced cell death.Calce-in-AM staining,FeRhoNox-1 staining,and C11 BODIPY 581/591 staining indicated that FUC obviously increased the levels of labile iron pool(LIP),Fe2+,and lipid reactive oxygen species(Lip ROS)in 143B cells.Chemical colorimetric analysis revealed that FUC markedly decreased intracellular Glutathi-one(GSH)contents.Real-time quantitative PCR showed that FUC dramatically reduced the mRNA lev-els of ferroptosis-related factors solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),while increasing the mRNA levels of prostaglandin endoperoxide synthase 2(PTGS2)and acyl-CoA synthetase long-chain family member 4(ACSL4).Western blotting analysis demonstrated that FUC significantly reduced the protein levels of SLC7A11 and GPX4,and the ratios of p-PI3K/PI3K,p-AktSer473/Akt,and p-AktThr308/Akt,but increased the protein level of ACSL4.Immunofluorescence staining showed that FUC obviously inhibited the nuclear translocation of p-AktSer473.The ferroptosis in-hibitor ferrostatin-1(Fer-1)and iron chelator deferoxamine(DFO)remarkably suppressed cell death in-duced by FUC in 143B cells.Additionally,the PI3K/Akt pathway activator 740Y-P significantly inhibi-ted FUC-induced iron overload and lipid peroxidation in 143B cells,and restored the protein levels of SLC7A11 and GPX4.In conclusion,FUC can induce ferroptosis of 143B cells by inhibiting the PI3K/Akt signaling pathway,which may be a potential target for the prevention and treatment of osteosarcoma.

OBJECTIVE To standardize the strategies for prevention and control of Chikungunya(CHIK)in healthcare in-stitutions so as to reduce the risk of transmission in the institutions.METHODS A working group comprising the ex-perts in hospital infection control,infectious diseases,and microbiology systematically reviewed domestic and international evidence and current guidelines,integrated China's vector ecology and healthcare realities,conducted two rounds of Delphi to achieve expert consensus,and graded the evidence and recommendation strength using the Oxford Centre for Evidence Based Medicine system.RESULTS The consensus issues 18 actionable recommendations on triage,patient mosquito-proof isolation,integrated vector control,protection of susceptible populations,environmental cleaning and disinfection,specimen management,medical textile handling,and outbreak emergency response,with each statement assigned an evi-dence level and recommendation strength.CONCLUSION This consensus is for the first time in China to provide evidence-graded strategies for control of CHIK in healthcare institutions,offering work flow-oriented,implementable guidance for clinicians,laboratorians,and infection-control personnel under different risk scenarios and enhancing the comprehensive coping capacity of the healthcare institutions.

Objective:To analyze the clinical phenotypes and genotypes of a family with posterior segment microphthalmia-retinoschisis and drusen syndrome.Methods:A pedigree investigation study was conducted.A family with four members across two generations treated at Shenzhen Eye Hospital in July 2021 was enrolled.Detailed ophthalmic examinations, including best corrected visual acuity (BCVA), intraocular pressure, slit-lamp microscopy, color fundus photography, optical coherence tomography (OCT), anterior segment OCT, fundus fluorescein angiography (FFA), and visual field tests were performed in the four members.Peripheral venous blood samples were collected from members for whole exome sequencing and data analysis.The pathogenicity of novel variant sites was assessed according to the ACMG guidelines.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shenzhen Eye Hospital (No.22KYPJ018).Written informed consent was obtained from each subject or the guardian.Results:The proband is a 14-year-old female with high hyperopia since childhood, BCVA of + 9.75 DS-0.75 DC×150°=0.9 and + 11.75 DS-1.25 DC×30°=0.7, corneal transverse diameters of 12.1 and 12.2 mm, anterior chamber depths of 2.56 and 2.92 mm, lens thicknesses of 3.92 and 3.94 mm, and axial lengths of 17.47 and 17.01 mm in the right and left eyes, respectively.Fundus photography revealed diffuse yellow-white drusen-like lesions with unclear borders in the mid-peripheral retina, while OCT showed retinoschisis in the inner nuclear layer and homogeneous mound-like elevations with hyperreflective dense spots under the retinal pigment epithelium.FFA demonstrated diffuse punctate transilllumination of the mid-peripheral retina in both eyes, and visual field tests revealed a general decrease in visual acuity.The proband's 8-year-old brother exhibited similar signs to the proband.The consanguineously married parents were phenotypically normal.Whole exome sequencing identified compound heterozygous mutations in the membrane frizzled-related protein ( MFRP) gene in the proband and her brother, c.1150_1151insC (p.His384Profs*8) in exon 5 and c. 498_499insC (p.Asn167Glnfs*34) in exon 10.The father carried the c. 498_499insC mutation, while the mother carried the c.1150_1151insC mutation.Both were frameshift mutations predicted to alter gene function.These novel mutations had not been reported in the ESP, 1 000 Genomes (Phase 3), or ExAC databases, indicating they are novel variants.The variants co-segregated with the disease and both were classified as pathogenic according to ACMG guidelines.Based on the clinical and genetic findings, the family was diagnosed with posterior segment microphthalmia-retinoschisis and drusen syndrome, inherited in an autosomal recessive manner. Conclusions:The MFRP gene mutations c. 1150_1151insC and c. 498_499insC are the pathogenic variants for the posterior segment microphthalmia-retinoschisis and drusen syndrome in this family, and these compound heterozygous mutations are reported for the first time.